Practice question

FGF8 from AER is critical maintenance factor for Sonic hedgehog expression in posterior ZPA. FGF8 signals through FGFR receptors activating ETS transcription factors Etv4 and Etv5 which bind conserved ZRS enhancer driving Shh transcription, and simultaneously induce Gremlin1 blocking BMP mediated repression of FGFs. Experimental removal of AER causes rapid Shh downregulation, whereas FGF bead implantation rescues Shh expression and restores posterior patterning. Thus FGF8 closes positive feedback ensuring prolonged SHH activity during digit specification window, coordinating proximal-distal growth with anterior-posterior patterning and maintaining polarizing activity.